tbuckley/cabot-search huggingface dataset:
E-Cigarettes, the FDA, Public Health, and Harm Reduction: A Response to the Open Peer Commentaries
Authors: Larisa Svirsky, Dana Howard, Micah L. Berman
Journal: The American Journal of Bioethics (2022)

This article refers to:Moral Wrongs, Epistemic Wrongs, and the FDAE-Cigarettes, the FDA’s Strategic Orientation, and Lessons from the Opioid CrisisExternal Dynamics Contextualizing the FDA’s Role in E-Cigarette RegulationStepping Up or Stepping Back: FDA Roles in Producing and Shaping Knowledge of Pediatric Covid-19 VaccinesE-Cigarette Use and Regulation: A Comparative Analysis between the United States, the UK, and ChinaAdvice on Vaping in the Face of Empirical and Ethical UncertaintyLimitations on the Capability of the FDA to AdviseHarm Reduction Ethics, Public Health, and the Manufacture of Doubt
Early Mobilization of Critical Care Patients — Still More to Learn
Authors: Marc Moss
Journal: New England Journal of Medicine (2022)

Each year, intensive care unit (ICU)–acquired weakness occurs in approximately 1 million critically ill patients who are undergoing mechanical ventilation worldwide.1 ICU-acquired weakness begins early in the course of critical illness and is related to multiple mechanisms, including deconditioning, myopathy, and neuropathy. Its development is associated with several deleterious outcomes, including increased mortality and diminished long-term quality of life.2 By improving muscle strength, endurance, and the performance of functional activities, early patient mobilization may be a treatment option for ICU-acquired weakness. However, previous studies examining early mobilization have shown conflicting results.3-7 As reported now in the Journal, the Treatment of . . .
Early Active Mobilization during Mechanical Ventilation in the ICU
Authors: Carol L Hodgson, Michael Bailey, Rinaldo Bellomo, Kathy Brickell, Tessa Broadley, Heidi Buhr, Belinda J Gabbe, Doug W Gould, Meg Harrold, Alisa M Higgins, Sally Hurford, Theodore J Iwashyna, Ary Serpa Neto, Alistair D Nichol, Jeffrey J Presneill, Stefan J Schaller, Janani Sivasuthan, Claire J Tipping, Steven Webb, Paul J Young
Journal: New England Journal of Medicine (2022)

Intensive care unit (ICU)-acquired weakness often develops in patients who are undergoing invasive mechanical ventilation. Early active mobilization may mitigate ICU-acquired weakness, increase survival, and reduce disability.We randomly assigned 750 adult patients in the ICU who were undergoing invasive mechanical ventilation to receive increased early mobilization (sedation minimization and daily physiotherapy) or usual care (the level of mobilization that was normally provided in each ICU). The primary outcome was the number of days that the patients were alive and out of the hospital at 180 days after randomization.The median number of days that patients were alive and out of the hospital was 143 (interquartile range, 21 to 161) in the early-mobilization group and 145 days (interquartile range, 51 to 164) in the usual-care group (absolute difference, -2.0 days; 95% confidence interval [CI], -10 to 6; P = 0.62). The mean (±SD) daily duration of active mobilization was 20.8±14.6 minutes and 8.8±9.0 minutes in the two groups, respectively (difference, 12.0 minutes per day; 95% CI, 10.4 to 13.6). A total of 77% of the patients in both groups were able to stand by a median interval of 3 days and 5 days, respectively (difference, -2 days; 95% CI, -3.4 to -0.6). By day 180, death had occurred in 22.5% of the patients in the early-mobilization group and in 19.5% of those in the usual-care group (odds ratio, 1.15; 95% CI, 0.81 to 1.65). Among survivors, quality of life, activities of daily living, disability, cognitive function, and psychological function were similar in the two groups. Serious adverse events were reported in 7 patients in the early-mobilization group and in 1 patient in the usual-care group. Adverse events that were potentially due to mobilization (arrhythmias, altered blood pressure, and desaturation) were reported in 34 of 371 patients (9.2%) in the early-mobilization group and in 15 of 370 patients (4.1%) in the usual-care group (P = 0.005).Among adults undergoing mechanical ventilation in the ICU, an increase in early active mobilization did not result in a significantly greater number of days that patients were alive and out of the hospital than did the usual level of mobilization in the ICU. The intervention was associated with increased adverse events. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; TEAM ClinicalTrials.gov number, NCT03133377.).
Rachel Clarke: Ukraine—how do you live in the face of death?
Authors: Rachel Clarke
Journal: BMJ (2022)

Rachel Clarke: Ukraine-how do you live in the face of death? Rachel Clarke specialty doctor in palliative medicineFor her first six months of work as a doctor in the small Ukrainian town of Sambir, Olena Parijchuk was paid precisely nothing.She and a small group of fellow physicians had an audacious plan-to transform a dilapidated tuberculosis sanitorium on the town's periphery into a 30 bed hospice.They toiled and painted and sawed and heaved, doctors-turned-labourers with more grit than sense."Some of my colleagues in Kyiv told me I was mad," Olena tells me, smiling broadly."And maybe I was.
Large-scale, closed-loop interrogation of neural circuits underlying cognition
Authors: Dion Khodagholy, Jose J. Ferrero, Jaehyo Park, Zifang Zhao, Jennifer N. Gelinas
Journal: Trends in Neurosciences (2022)

Cognitive functions are increasingly understood to involve coordinated activity patterns between multiple brain regions, and their disruption by neuropsychiatric disorders is similarly complex. Closed-loop neurostimulation can directly modulate neural signals with temporal and spatial precision. How to leverage such an approach to effectively identify and target distributed neural networks implicated in mediating cognition remains unclear. We review current conceptual and technical advances in this area, proposing that devices that enable large-scale acquisition, integrated processing, and multiregion, arbitrary waveform stimulation will be critical for mechanistically driven manipulation of cognitive processes in physiological and pathological brain networks.
Structural and functional analyses of a GPCR-inhibited ion channel TRPM3
Authors: Chen Zhao, Roderick MacKinnon
Journal: Neuron (2022)

G-protein coupled receptors (GPCRs) govern the physiological response to stimuli by modulating the activity of downstream effectors, including ion channels. TRPM3 is an ion channel inhibited by GPCRs through direct interaction with G protein (Gβγ) released upon their activation. This GPCR-TRPM3 signaling pathway contributes to the analgesic effect of morphine. Here, we characterized Gβγ inhibition of TRPM3 using electrophysiology and single particle cryo-electron microscopy (cryo-EM). From electrophysiology, we obtained a half inhibition constant (IC50) of ∼240 nM. Using cryo-EM, we determined structures of mouse TRPM3 expressed in human cells with and without Gβγ and with and without PIP2, a lipid required for TRPM3 activity, at resolutions of 2.7-4.7 Å. Gβγ-TRPM3 interfaces vary depending on PIP2 occupancy; however, in all cases, Gβγ appears loosely attached to TRPM3. The IC50 in electrophysiology experiments raises the possibility that additional unknown factors may stabilize the TRPM3-Gβγ complex.
Contrastive domain adaptation with consistency match for automated pneumonia diagnosis
Authors: Yangqin Feng, Zizhou Wang, Xinxing Xu, Yan Wang, Huazhu Fu, Shaohua Li, Liangli Zhen, Xiaofeng Lei, Yingnan Cui, Jordan Sim Zheng Ting, Yonghan Ting, Joey Tianyi Zhou, Yong Liu, Rick Siow Mong Goh, Cher Heng Tan
Journal: Medical Image Analysis (2022)
Injectable and photocurable CAR-T cell formulation enhances the anti-tumor activity to melanoma in mice
Authors: Weilin Zhou, Sibei Lei, Mei Liu, Dan Li, Yong Huang, Xiaoyi Hu, Jinrong Yang, Jing Li, Maorong Fu, Mengxi Zhang, Fengling Wang, Jiaqian Li, Ke Men, Wei Wang
Journal: Biomaterials (2022)
Autism incidence and spatial analysis in more than 7 million pupils in English schools: a retrospective, longitudinal, school registry study
Authors: Andres Roman-Urrestarazu, Justin C Yang, Robin van Kessel, Varun Warrier, Guillaume Dumas, Hannah Jongsma, Gabriel Gatica-Bahamonde, Carrie Allison, Fiona E Matthews, Simon Baron-Cohen, Carol Brayne
Journal: The Lancet Child & Adolescent Health (2022)
Implementing and Assessing a Resident Diversity Council to Address the Need for a Diverse Clinical Workforce
Authors: Cody Gathers, Camila M. Mateo, Colin Sox
Journal: JAMA Network Open (2022)

Minoritized racial and ethnic groups remain underrepresented in medicine (UIM) compared with the general population. Although many residency programs want to train a diverse group of individuals, methods for implementation are not fully established.To describe the implementation and restructuring of the Boston Combined Residency Program (BCRP) Diversity Council and evaluate the association between restructuring the BCRP Diversity Council and the number of UIM interns.A retrospective cohort study was conducted on a large academic pediatric residency program at Boston Children's Hospital and Boston Medical Center. Interns who matched in the BCRP from March 17, 2011, to March 18, 2021, were included. Interns who matched in an affiliated medicine-pediatrics residency were excluded because they are not universally exposed to the same recruitment efforts as individuals in the other BCRP tracks.Because the BCRP Diversity Council was restructured in 2016, 2011-2016 was defined as the prerestructuring era and 2017-2021 as the postrestructuring era.The primary outcome was the proportion of interns who self-identified as UIM.A total of 516 BCRP interns from 2011 to 2021 were included. A total of 62 individuals (12.0%) identified as racial and ethnic identities UIM (ie, American Indian/Alaska Native, Black/African American, Hispanic/Latino, and Native Hawaiian/Pacific Islander). During the 6-year prerestructuring Diversity Council era, 27 of the 275 BCRP interns (9.8%) were UIM; 35 of 241 BCRP interns (14.5%) were UIM during the 5-year restructured Diversity Council era (χ2﻿ P = .10).In this cohort study, the number of UIM interns was higher after the BCRP Diversity Council was restructured, although the difference was not statistically significant. As the magnitude of the Diversity Council's influence is multidimensional, perhaps studying additional aspects would have better captured its impact. The BCRP Diversity Council has expanded innovative recruitment initiatives, supported efforts to improve the resident experience, and collaborated with the residency and institutional leadership to promote an inclusive and antiracist learning environment.
Association Between Smoking, Smoking Cessation, and Mortality by Race, Ethnicity, and Sex Among US Adults
Authors: Blake Thomson, Jonathan Emberson, Ben Lacey, Sarah Lewington, Richard Peto, Ahmedin Jemal, Farhad Islami
Journal: JAMA Network Open (2022)

Importance Patterns of cigarette smoking and smoking cessation vary considerably across demographic groups in the US, but there is limited evidence on whether the hazards of smoking and benefits of quitting vary across these groups. Population-specific evidence on the benefits of quitting smoking may motivate cessation among groups historically underrepresented in medical research. Objective To quantify the association between smoking, smoking cessation, and mortality by race, ethnicity, and sex. Design, Setting, and Participants This nationally representative, prospective cohort study used data from the US National Health Interview Survey collected via questionnaire between January 1997 and December 2018 among adults aged 25 to 84 years at recruitment. Participants were followed up for cause-specific mortality through December 31, 2019. Exposures Self-reported smoking status at recruitment, age at quitting smoking, and years since quitting smoking. Main Outcomes and Measures The main outcomes were all-cause mortality and mortality from cancer, cardiovascular disease, and lower respiratory disease. Adjusted mortality rate ratios comparing never, former, and current smokers were calculated using Cox proportional hazards regression. Weighted analyses were conducted by race, ethnicity, and sex as reported by participants. Results Among the 551 388 participants in the main analyses, the mean (SD) age at recruitment was 48.9 (15.3) years; 307 601 (55.8%) were women, 87 207 (15.8%) were Hispanic, 75 545 (13.7%) were non-Hispanic Black, 355 782 (64.5%) were non-Hispanic White, and 32 854 (6.0%) identified as other non-Hispanic race and ethnicity. There were 74 870 deaths among participants aged 25 to 89 years during follow-up (36 792 [49.1%] among men; 38 078 [50.9%] among women). The all-cause mortality rate ratio (RR) for current vs never smoking was 2.80 (95% CI, 2.73-2.88) overall. The RRs were similar by sex but varied by race and ethnicity: Hispanic, 2.01 (95% CI, 1.84-2.18); non-Hispanic Black, 2.19 (95% CI, 2.06-2.33); non-Hispanic White, 3.00 (95% CI, 2.91-3.10); and other non-Hispanic race and ethnicity, 2.16 (95% CI, 1.88-2.47). When comparing those who quit smoking before age 45 years with never smokers, all-cause mortality RRs were 1.15 (95% CI, 1.03-1.28) among Hispanic individuals, 1.16 (95% CI, 1.07-1.25) among non-Hispanic Black individuals, 1.11 (95% CI, 1.08-1.15) among non-Hispanic White individuals, and 1.17 (95% CI, 0.99-1.39) among other non-Hispanic individuals. Conclusions and Relevance In this prospective cohort study, among men and women from diverse racial and ethnic groups, current smoking was associated with at least twice the all-cause mortality rate of never smoking. Quitting smoking, particularly at younger ages, was associated with substantial reductions in the relative excess mortality associated with continued smoking.
Quitting Smoking by Age 35 Years—A Goal for Reducing Mortality
Authors: John P. Pierce
Journal: JAMA Network Open (2022)

Blake Thomson, DPhil; Jonathan Emberson, PhD; Ben Lacey, MBChB, DPhil; Sarah Lewington, DPhil; Richard Peto, MSc; Ahmedin Jemal, DVM, PhD; Farhad Islami, MD, PhD
Bone Metastasis Initiation Is Coupled with Bone Remodeling through Osteogenic Differentiation of NG2+ Cells
Authors: Weijie Zhang, Zhan Xu, Xiaoxin Hao, Tiancheng He, Jiasong Li, Yichao Shen, Kai Liu, Yang Gao, Jun Liu, David G. Edwards, Aaron M. Muscarella, Ling Wu, Liqun Yu, Longyong Xu, Xi Chen, Yi-Hsuan Wu, Igor L. Bado, Yunfeng Ding, Sergio Aguirre, Hai Wang, Zbigniew Gugala, Robert L. Satcher, Stephen T.C. Wong, Xiang H.-F. Zhang
Journal: Cancer Discovery (2022)

Abstract The bone microenvironment is dynamic and undergoes remodeling in normal and pathologic conditions. Whether such remodeling affects disseminated tumor cells (DTC) and bone metastasis remains poorly understood. Here, we demonstrated that pathologic fractures increase metastatic colonization around the injury. NG2+ cells are a common participant in bone metastasis initiation and bone remodeling in both homeostatic and fractured conditions. NG2+ bone mesenchymal stem/stromal cells (BMSC) often colocalize with DTCs in the perivascular niche. Both DTCs and NG2+ BMSCs are recruited to remodeling sites. Ablation of NG2+ lineage impaired bone remodeling and concurrently diminished metastatic colonization. In cocultures, NG2+ BMSCs, especially when undergoing osteodifferentiation, enhanced cancer cell proliferation and migration. Knockout of N-cadherin in NG2+ cells abolished these effects in vitro and phenocopied NG2+ lineage depletion in vivo. These findings uncover dual roles of NG2+ cells in metastasis and remodeling and indicate that osteodifferentiation of BMSCs promotes metastasis initiation via N-cadherin–mediated cell–cell interaction. Significance: The bone colonization of cancer cells occurs in an environment that undergoes constant remodeling. Our study provides mechanistic insights into how bone homeostasis and pathologic repair lead to the outgrowth of disseminated cancer cells, thereby opening new directions for further etiologic and epidemiologic studies of tumor recurrences. This article is highlighted in the In This Issue feature, p. 247
Clinical Trials Design, Scientific Rigor, and Higher-Level Evidence in Surgery
Authors: Kamal M. F. Itani, Melina R. Kibbe
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder
Authors: Layla Thurston, Tia Hunjan, Natalie Ertl, Matthew B. Wall, Edouard G. Mills, Sofiya Suladze, Bjial Patel, Emma C. Alexander, Beatrice Muzi, Paul A. Bassett, Eugenii A. Rabiner, Paul Bech, David Goldmeier, Ali Abbara, Alexander N. Comninos, Waljit S. Dhillo
Journal: JAMA Network Open (2022)

Importance Despite being the most common female sexual health complaint worldwide, current treatment options for hypoactive sexual desire disorder (HSDD) are limited in their safety and effectiveness. The hormone kisspeptin is a key endogenous activator of the reproductive hormonal axis with additional emerging roles in sexual and emotional behavior; however, its effects in women with HSDD are unknown. Objective To test the hypothesis that kisspeptin enhances sexual and attraction brain processing in women with HSDD. Design, Setting, and Participants This randomized clinical trial was double-masked and placebo controlled with a 2-way crossover. The trial was conducted in a university research setting in the UK from October 2020 to April 2021. Eligible participants were premenopausal women with HSDD. Functional neuroimaging, psychometric, and hormonal analyses were employed to investigate the effects of kisspeptin administration on brain processing, in response to erotic stimuli (erotic videos) and facial attraction (face images of varying attractiveness). Data were analyzed from May to December 2021. Interventions A 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate placebo infusion. Main Outcomes and Measures Blood oxygen level–dependent responses across the whole brain and regions of interest during kisspeptin vs placebo administration in response to erotic and facial attraction stimuli. Results Of the 40 participants who were randomized, 32 women completed both kisspeptin and placebo visits, with a mean (SE) age of 29.2 (1.2) years. Kisspeptin administration resulted in modulations in sexual and facial attraction brain processing (deactivation of the left inferior frontal gyrus: Z max, 3.76; P = .01; activation of the right postcentral and supramarginal gyrus: Z max, 3.73; P &amp;amp;lt; .001; deactivation of the right temporoparietal junction: Z max 4.08; P = .02). Furthermore, positive correlations were observed between kisspeptin-enhanced hippocampal activity in response to erotic videos, and baseline distress relating to sexual function ( r = 0.469; P = .007). Kisspeptin’s enhancement of posterior cingulate cortex activity in response to attractive male faces also correlated with reduced sexual aversion, providing additional functional significance ( r = 0.476, P = .005). Kisspeptin was well-tolerated with no reported adverse effects. Conclusions and Relevance These findings lay the foundations for clinical applications for kisspeptin in women with HSDD. Trial Registration ISRCTN trial registry identifier: ISRCTN17271094
Association of Exposure to Wildfire Air Pollution With Exacerbations of Atopic Dermatitis and Itch Among Older Adults
Authors: Raj P. Fadadu, Marcus Green, Nicholas P. Jewell, Barbara Grimes, Jason Vargo, Maria L. Wei
Journal: JAMA Network Open (2022)

This cross-sectional study evaluates the association of exposure to wildfire air pollution with exacerbations of atopic dermatitis and itch among adults aged 65 years or older.
Measuring and Achieving Child Well-being—Yardsticks, Barometers, and Canaries in the Coalmine
Authors: Kate E. Pickett
Journal: JAMA Network Open (2022)

Nathaniel W. Anderson, PhD; Daniel Eisenberg, PhD; Neal Halfon, MD, MPH; Anna Markowitz, PhD; Kristin Anderson Moore, PhD; Frederick J. Zimmerman, PhD
Autoantibody-mediated Macrophage Dysfunction in Patients with Severe Asthma with Airway Infections
Authors: Kiho Son, Kate Miyasaki, Brittany Salter, Dessi Loukov, Joseph Chon, Nan Zhao, Katherine Radford, Chynna Huang, Nicola LaVigne, Anna Dvorkin-Gheva, Paige Lacy, Terence Ho, Dawn M. E. Bowdish, Parameswaran Nair, Manali Mukherjee
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Localized autoimmune responses have been reported in patients with severe eosinophilic asthma, characterized by eosinophil degranulation and airway infections. Objective: To determine the presence of autoantibodies against macrophage scavenger receptors within the airways and their effects on macrophage function and susceptibility to infection. Methods: Anti-EPX (eosinophil peroxidase), anti-MARCO (macrophage receptor with collagenous structure) IgG titers, and T1 and T2 (type 1/2) cytokines were measured in 221 sputa from 143 well-characterized patients with severe asthma. Peripheral monocytes and MDMs (monocyte-derived macrophages) isolated from healthy control subjects were treated with immunoprecipitated immunoglobulins from sputa with high anti-MARCO titers or nonspecific IgG to assess uptake of Streptococcus pneumoniae or response to the bacterial product LPS. Measurements and Main Results: Anti-MARCO IgG was detected in 36% of patients, with significantly higher titers (up to 1:16) in patients with mixed granulocytic sputa, indicative of airway infections. Multivariate regression analysis confirmed increased frequency of degranulation (free eosinophil granules), increased blood eosinophils (indicative of high T2 burden), increased sputum total cell count, peripheral blood leukocytes (indicative of infection), and lymphopenia were associated with increased anti-MARCO IgG titers; IL-15 (odds ratio [OR], 1.79; confidence interval [CI], 1.19-2.70), IL-13 (OR, 1.06; CI, 1.02-1.12), and IL-12p70 (OR, 3.34; CI, 1.32-8.40) were the associated cytokines. Patients with anti-MARCO antibodies had higher chances of subsequent infective versus eosinophilic exacerbations (P = 0.01). MDMs treated with immunoprecipitated immunoglobulins (anti-MARCO+ sputa) had reduced bacterial uptake by 39% ± 15% and significantly reduced release of IL-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF) (P < 0.05) in response to an LPS stimulus. Conclusions: Autoantibodies against macrophage scavenger receptors in eosinophilic asthma airways may impede effective host defenses and lead to recurrent infective bronchitis.